How to sober up? Do you have the enzyme?

Author: Zhou Rui, Shandong Yantai Yuhuangding Hospital

Reviewer: Liu Wendong, Chief Physician, Qingdao Municipal Hospital, Shandong

Wine culture is not only a part of social activities, but also a carrier of historical traditions. From ancient times to the present, winemaking and wine tasting have gradually penetrated into the lives of more and more people, becoming a way to celebrate, communicate and relax. However, people's attitudes towards wine culture have also evolved over time. At lively gatherings, people are immersed in the pleasure and relaxation brought by alcohol, with laughter and clinking of glasses. But after the banquet, they have to face the consequences of alcohol, such as common symptoms such as headaches, nausea, and fatigue. In our bodies, there is a "mysterious team" - enzymes that sober up. These tiny but powerful biological molecules work silently in the body, converting alcohol into harmless substances, helping us get rid of the troubles of alcohol. Let us explore these magical enzymes together and unveil their mysterious veil.

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1. Why do some people get drunk after just one sip, while others can drink a thousand cups without getting drunk?

The "culprit" of blushing after drinking is acetaldehyde accumulated in the blood, not alcohol. Then some people will definitely be curious: "I obviously drank alcohol, what does it have to do with acetaldehyde?" In fact, after we drink alcohol, alcohol is first converted into acetaldehyde in the body under the action of alcohol dehydrogenase (ADH) in the liver, and further converted into acetic acid under the action of acetaldehyde dehydrogenase (ALDH2). Is "acetaldehyde" discovered in this process? Acetaldehyde can dilate blood vessels, causing facial redness and accelerated heartbeat. ALDH2 is used to reduce acetaldehyde concentration. It is a mitochondrial enzyme that participates in detoxification and can convert acetaldehyde into acetic acid and excrete it from the body. If ALDH2 functions normally, acetaldehyde is quickly converted into acetic acid. However, some people carry a mutant gene that causes ALDH2 dysfunction, which is common in Asian populations. After they drink, acetaldehyde cannot be effectively converted and accumulates in the body, causing symptoms such as blushing and headaches.

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2. Can I drink alcohol? Can I become more alcoholic through practice?

As we mentioned earlier, after drinking, alcohol is first converted into acetaldehyde by alcohol dehydrogenase (ADH) in the liver, and acetaldehyde is then converted into acetic acid by acetaldehyde dehydrogenase (ALDH2), and finally excreted as carbon dioxide and water. Usually, people's ADH activity does not differ much, but ALDH2 activity varies greatly, and the latter's activity is the main factor that determines the amount of alcohol consumed. The amount of alcohol consumed depends on the speed at which acetaldehyde is cleared, which depends on normal ALDH2, and the enzyme is encoded by genes, so everyone is destined to drink before birth. The ALDH2 gene is encoded by a nuclear gene on chromosome 12 and is located in the mitochondria. In East Asian populations, the ALDH2 gene has obvious single nucleotide polymorphisms, concentrated in the rs671 site. Mutations in this site reduce the decomposition of acetaldehyde, leading to acetaldehyde accumulation after drinking, causing adverse reactions such as flushing and tachycardia.

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ALDH2 has three genotypes: Glu504Glu is homozygous for glutamate at position 504 of ALDH2 (ALDH2*1/*1), with normal enzyme activity; Glu504Lys is heterozygous for glutamate/lysine at position 504 of ALDH2 (ALDH2*1/*2), with poor enzyme activity; Lys504Lys is homozygous for lysine at position 504 of ALDH2 (ALDH2*2/*2), with no enzyme activity. In the Chinese population, ALDH2*1/*1 accounts for the largest proportion, with differences between regions, but mutant ALDH2*1/*2 also accounts for a large proportion.

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Some people who blush when drinking believe that increasing the amount of alcohol they drink can improve their tolerance to alcohol. In fact, the genotype cannot be changed, and the body's tolerance to alcohol will not increase. "Increasing your alcohol tolerance" is a burden on the body's organs, and the damage caused by alcohol to the stomach, esophagus, liver, kidneys, etc. is irreversible.

3. As the saying goes, "A little drinking cheers you up, but too much drinking harms your body." Is moderate drinking really good for your health?

For thousands of years, drinking has been part of our social culture. From dinner parties to wedding banquets, celebrations and commemorations, drinking is always necessary. "A little drinking can make you happy, but too much drinking can harm you." We have heard this sentence since we were young, and we always think that drinking a little alcohol is not a big deal. However, in fact, from the first sip, alcohol will affect the body, even if we don't realize it. Drinking is harmful to health, and there is no so-called "safe amount". So, a little drinking can also harm your body!

Alcohol affects our body and mind, reducing our judgment and physical functions. Even a small amount of alcohol intake can have harmful effects on different organs, including the brain, heart, liver and pancreas, as well as the immune and digestive systems. Alcohol is a toxic, psychoactive, and addictive substance. It was classified as a Class 1 carcinogen by the International Agency for Research on Cancer decades ago - the highest risk type of carcinogen! Alcohol causes at least 7 types of cancer, such as colon cancer and breast cancer. Alcohol can cause cancer through a variety of biological mechanisms. On the one hand, alcohol produces acetaldehyde during metabolism in the human body. Acetaldehyde is a strong carcinogen that can directly bind to DNA in cells, causing DNA damage and mutations. If these damage and mutations cannot be repaired in time, they may cause cell cancer. On the other hand, alcohol may affect the metabolism of estrogen in the body. Long-term drinking may lead to increased estrogen levels, thereby increasing the risk of breast cancer. At the same time, alcohol may interfere with the balance of other hormones, thereby affecting cell growth and differentiation and increasing the possibility of cancer. In addition, alcohol can inhibit the function of the immune system, reducing the body's ability to monitor and eliminate cancer cells. Long-term drinking can also lead to chronic inflammation, which is closely related to the occurrence and development of various cancers. In addition, alcohol can interfere with the body's absorption and metabolism of some important nutrients, such as vitamin A, vitamin C, vitamin E and other antioxidants and folic acid. Lack of these nutrients will increase the risk of cell cancer. At the same time, alcohol may also affect the balance of intestinal flora and change the microenvironment in the intestine.

This means that any alcoholic beverage, regardless of its price and quality, has a risk of cancer. In addition, drinking alcohol also increases the risk of cardiovascular disease, liver disease, cognitive decline, and impaired mental state.

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4. Aldehyde dehydrogenase: the body’s hangover-detoxifying hero and also the chemical guardian of nitroglycerin?

Nitroglycerin is commonly used as a treatment for heart disease, dilating blood vessels and improving blood flow by releasing nitric oxide. Aldehyde dehydrogenase (ALDH2) has been found to encode nitrate esterase, which can participate in the metabolism of nitroglycerin and help it release nitric oxide, thereby producing a therapeutic effect. When angina pectoris occurs, sublingual nitroglycerin tablets are the conventional first-line treatment, but its metabolic capacity varies from person to person. There is a close relationship between ALDH2 genotype and nitroglycerin metabolism, which is particularly important in drug treatment. ALDH2 gene mutations may affect an individual's ability to metabolize nitroglycerin, thereby affecting its therapeutic effect and safety. For individuals with mutant genes such as ALDH2*2 (including ALDH2*1/*2 and ALDH2*2/*2), they may show lower nitroglycerin metabolism, resulting in reduced drug activity in the body and weakened therapeutic effects. Therefore, when using nitroglycerin to treat cardiovascular disease, it is recommended that individuals first undergo genetic testing to understand their ALDH2 genotype in order to determine the best treatment plan and dosage. At the same time, doctors should also consider individual genotype information when prescribing drugs to ensure the effectiveness and safety of the drugs. This individualized treatment strategy can maximize the treatment effect and reduce the occurrence of adverse drug reactions, thereby better protecting the health of patients.

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In short, ALDH2 plays an important role in the human body. It is involved in the metabolism of alcohol and is closely related to the metabolism of nitroglycerin. In alcohol metabolism, ALDH2 helps convert acetaldehyde into acetic acid, reducing the harm of alcohol to the body, so it is called the "alcohol detoxification enzyme." In nitroglycerin metabolism, ALDH2 also plays a role, assisting nitroglycerin in releasing nitric oxide, thereby dilating blood vessels and improving blood flow. This dual function makes ALDH2 an important chemical regulator in the body, not only playing a role in the process of detoxification, but also participating in the treatment of cardiovascular diseases. Therefore, a deep understanding of the function of ALDH2 will help formulate individualized drug treatment plans, improve treatment effects, and reduce the occurrence of adverse reactions.